• 한국약용작물학회지
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• 제16권5호
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• pp.341-348
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• 2008

Cholesterol acyltransferase (ACAT) catalyzes the acylation of cholesterol to cholesteryl ester with long chain fatty acids and ACAT inhibition is a useful strategy for treating hypercholesterolemia or atherosclerosis. Inhibitory effects on ACAT of the MeOH extracts prepared from 163 edible plants were evaluated. 15 species out of 163 species exhibited higher than 50% of inhibition on the hACAT-1 and 9 species exhibited higher than 50% of inhibition on the hACAT-2 activity at their concentration of $100\;{\mu}g/mL$.

• 한국미생물·생명공학회지
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• 제21권6호
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• pp.600-608
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• 1993

About 1, 300 strains isolated from soil were evaluated for acyl-CoA:cholesterol acyltransferase (ACAT) inhibition activity. About 4.0% of actinomycetes and 3.6% of fungi showed greater than 50% inhibition activity, respectively. However, none of the isolated bacteria exhibited inhibition activity more than 50%. Among them, one Streptomyces sp. A-3 showed a higher ACAT inhibition activity in culture broth. Isolation of the ACAT inhibitor (AI-3) was achieved by Amberlite XAD-7 column, silica-gel column, Sephadex LH-20 gel-filtration and reverse phase HPLC.

• 생약학회지
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• 제30권4호
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• pp.384-396
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• 1999

Acyl-CoA: Cholesterol Acyltransferase (ACAT) is a key enzyme responsible for cholesteryl ester formation in atherogenesis and in cholesterol absorption from the intestines. In addition under pathological conditions, formation and accumulation of cholesteryl ester as lipid droplets by ACAT within macrophages constitute a characteristic feature of early lesions of atherosclerotic plaques. ACAT inhibitors are expected to be effective for treatment of atherosclerosis and hypercholesterolemia. ACAT inhibitors of natural origin have been rarely reported. In our screening program for ACAT inhibitors, 303 plants were extracted with methanol or ethanol, and screened for the inhibitory activity against ACAT from the rat liver microsome. Extracts of 13 plants including Quercus aliena, Diospyros kaki, Platycarya strobilacea and Hibiscus syriacus inhibited more than 90% of ACAT activity and 43 samples in alcohol extracts such as Magnolia obovata and Panax ginseng also inhibited more than 70% of ACAT activity at a concentration of $100\;{\mu}g/ml$.

• Bulletin of the Korean Chemical Society
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• 제29권3호
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• pp.615-619
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• 2008

Eight triterpenoids, six lanostanes 1-6, one lupenane 7, and one oleanane 8, were isolated by bioactivity-guided fractionation of the ethylacetate extract from roots of Glycine max (L.) Merr. All isolated compounds were examined for their inhibitory activities against human ACAT-1 (hACAT-1) and human ACAT-2 (hACAT-2). Among them, three triterpenoids showed potent hACAT inhibitory activities, (24R)-ethylcholest-5-ene-3,7-diol (1) and 3b -hydroxylup-20(29)-en-28-oic acid (7) exhibited more potent inhibitory activity against hACAT-1 (1: IC50 = 25.0 1.2 and 7: IC50 = 11.5 0.4 m M) than hACAT-2 (1: IC50 = 102.0 5.4 and 7: IC50 = 33.9 3.7 m M), respectively. Interestingly, 5a ,8a -epidioxy-24(R)-methylcholesta-6,22-diene-3b -ol (4) has proven to be a specific inhibitor against hACAT-1 (IC50 = 38.7 0.8 m M) compared to hACAT-2 (IC50 >200). In conclusion, this is the first study to demonstrate that triterpenoids of G. max have potent inhibitory activities against hACAT-1 and hACAT-2.

• Journal of Applied Biological Chemistry
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• 제52권4호
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• pp.187-194
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• 2009

참당귀 뿌리로부터 2종의 pyranocoumarin 성분을 분리하고 그들의 구조는 NMR 분석에 의해 각각 decursinol angelate(1), decursin(2)로 결정하였다. 이들 화합물에 대하여 hACAT 저해활성을 검정해본 결과, decursinol angelate(1)가 약한 저해활성을 나타낸 반면 decursin(2)은 hACAT1와 hACAT2에 대하여 $IC_{50}$ 값이 각각 137, $168\;{\mu}M$로서 우수한 저해활성을 나타내었다. 한편, 참당귀의 뿌리를 비롯한 꽃, 종자, 잎 등 여러부위에서 decursinol angelate(1), decursin(2)를 정량분석하였는데, 이때 LC/MS/MS(ESI, positive ion mode, MRM mode) 분석을 이용하였다. Decursinol angelate의 함량은 뿌리>잎>종자>꽃 순으로 높았으며, decursin의 함량은 뿌리>종자>꽃>잎 순으로 높게 측정되었다. 이상의 결과들은, 참당귀의 decursin이 동맥경화와 같은 심혈관 질환의 개선과 치료를 위해 유용하게 이용될 수 있음을 시사하였다. 또한 뿌리 이외에 그 동안 이용되지 않고 있던 참당귀 꽃, 잎과 같은 비상용부위에도 기능성물질인 decursin, decursinol angelate이 상당량 함유되어 있음이 구명되어 이러한 부위도 새로운 천연 기능성 소재로서 활용될 수 있음을 기대할 수 있었다.

• Archives of Pharmacal Research
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• 제29권3호
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• pp.191-194
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• 2006

Twigs from llex macropoda were extracted with MeOH, and the concentrated extracts were partitioned with $CH_2Cl_2$, EtOAc, n-BuOH, and $H_2O$. Repeated column chromatography of the $CH_2Cl_2$ fraction ultimately resulted in the isolation of two compounds, via activity-guided fractionation, using ACAT inhibitory activity measurements. According to the physico-chemical data, the chemical structures of these isolated compounds were identified as lupeol (1) and betulin (2). Compounds 1 and 2 were shown to inhibit the activity of hACAT-1 and hACAT-2 in a dose-dependent manner, and compounds 1 and 2 inhibited hACAT-1 with $IC_{50}$ values of 48 and $83{\mu}M$, respectively.

• 한국식생활문화학회지
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• 제4권2호
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• pp.185-189
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• 1989

Effect of perilla oil on the fatty acid composition, ACAT and HMG-CoA reductase in the liver microsomes, or cholesterol and protein in serum of rabbit were examined. 1. The content of total protein in serum was almost same amount of both groups, but ${\alpha_1}-globulin$ and r-globuline were incresed or ${\beta}-globulin$ was decresed compared with control. 2. The content of high density lipoprotein incresed, and the content of low density lipoprotein decresed in lipoprotein. 3. Total cholesterol and triglyceride were decresed, and the content of phospholipid was incresed. 4. Perilla oil did not effect for changing blood glucose and $Na^+,\;K^+$ electrolytes. 5. Perilla oil did not effect for changing serum GOT and GPT in rabbit. 6. The activity of ACAT decresed and the activity of HMG-CoA reductase incresed. The activity of ACAT and HMG-CoA reductase in liver microsomes were reciprocal. 7. There were arachidonic acid 20:4, eicosapentaenoic acid 20:5, and docosahexaenoic acid 22:6 in the liver microsomes of rabbits. These highly polyunsaturated fatty acids were convented from linolenic acid 18:3 n-3.

• Journal of Applied Biological Chemistry
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• 제49권2호
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• pp.57-61
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• 2006

Isoflavones 1-3 and pterocarpans 4-8 were isolated from methanol extract of roots of Glycine max. In inhibitory effect against human acyl-CoA:cholesterol acytransferase (ACAT)-1 and ACAT-2, glyceollin I 5 showed potent hACAT-1 ($IC_{50}=299.0{\mu}M$) and hACAT-2 ($IC_{50}=82.7{\mu}M$) inhibitory activities.

• The Korean Journal of Physiology and Pharmacology
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• 제23권1호
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• pp.37-45
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• 2019

To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly ${\beta}$-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-ketoacid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other $K_{ATP}$ channel openers.

• Natural Product Sciences
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• 제15권2호
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• pp.110-113
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• 2009

Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays important roles in intestinal absorption of cholesterol, hepatic production of lipoproteins and accumulation of cholesteryl ester within macrophages and smooth muscle cells. In our study, eight polyacetylenes (1 - 8), were isolated from the roots of Gymnaster koraiensis, and their chemical structures were identified on the basis of spectroscopic analysis and mass. Compound 2 with the (10S)-15,16-epoxy group in skeleton strongly inhibited ACAT enzyme with $IC_{50}$ value of 35.8 ${\mu}g$/mL, meanwhile the other compounds displayed significant inhibition of ACAT enzyme with the $IC_{50}$ values from 45.5 to 55.1 ${\mu}g$/mL.